Oral mucositis

Oral mucosal membranes provide a port for systemic therapy as weU. Nitroglycerin sublingual tablets (Nitrostat) abort acute mgina attacks methyl-testosterone [58-18-4] buccal tablets (Android 5) are indicated for testosterone [58-22-0] replacement therapy (39) md nicotine [54-11-5] gum (Nicorette) aids in smoking cessation. 

Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. New Engl J Med 2004 351 2590-2598. 

Oral Mucosal Drug Delivery, edited by Michael J. Rathbone... 

The expression of recombinant proteins in cells in which they do not naturally occur is termed heterologous protein production (Chapter 3). The first biopharmaceutical produced by genetic engineering to gain marketing approval (in 1982) was recombinant human insulin (tradename Humulin ), produced in E. coli. An example of a more recently approved biopharmaceutical that is produced in E. coli is that of Kepivance, a recombinant keratinocyte growth factor used to treat oral mucositis (Chapter 10). Many additional examples are provided in subsequent chapters. 

Kepivance (palifermin, rKGF) Severe oral mucositis Amgen... 

The initial trial establishing safety and efficacy was a randomized, placebo-controlled study involving 212 patients. The treated group received 60 pg kg-1 day-1 of the product for 6 days. The primary end-point measured was the number of days during which the patients experienced severe oral mucositis, which treatment reduced from 9 to 3 days. The incidence of mucositis was also reduced from 98 per cent to 63 per cent. 

Holmgren, J., N. Lycke, C. Czerkinsky, Cholera-Toxin and Cholera-B Subunit as Oral Mucosal Adjuvant and Antigen Vector Systems, Vaccine. 11, 1179, 1993. 

Tests Oral Mucosal Trans- dermal Dermal/ topical Paren- teral Inhalation/ intranasal Ocular... 

Table taken from Squier et at. 1996 [125]. Copyright (1996) From Oral Mucosal Drug Delivery, by Michael J. Rathbone (Ed.). Reproduced by permission of Routledge/Taylor Francis Group, LLC. 

Addy M (1980) The oral mucosal absorption and tissue distribution of triamcinolone acetonide in the dog studied by autoradiography. Arch Oral Biol 25 809-817... 

Ganem-Quintanar A, Quintanar-Guerrero D, Falson-Rieg F, Buri P (1998) Ex vivo oral mucosal permeation of lidocaine hydrochloride with sucrose fatty acid esters as absorption enhancers. Int J Pharm 173 203-210... 

Kimura T, Yarnano H, Tanaka A, Matsumura T, Ueda M, Ogawara K, Higaki K (2002) Transport of D-glucose across cultured stratified cell layer of human oral mucosal cells. J Pharm Pharmacol 54 213-219... 

Kurosaki Y, Yano K, Kimura T (1997) Perfusion cells for studying regional variation in oral-mucosal permeability in humans. I Kinetic aspects in oral-mucosal absorption of alkylparabens. Pharm Res 14 1241-1245... 

Squier CA, Wertz PW (1996) Structure and function of the oral mucosa and implications for drug delivery. In Rathbone MJ (ed.), Oral Mucosal Drug Delivery. Marcel Dekker, New York, pp 1-26... 

Squier CA, Kremer MJ, Bruskin A, Rose A, Haley JD (1999) Oral mucosal permeability and stabihty of transforming growth factor beta-3 in vitro. Pharm Res 16 1557-1563... 

Sveinsson SJ, Mezei M (1992) In vitro oral mucosal absorption of liposomal triamcinolone acetonide. Pharm Res 9 1359-1361... 

Tucker IG (1988) A method to study the kinetics of oral mucosal drug absorption from solutions. J Pharm Pharmacol 40 679-683... 

Yamahara H, Suzuki T, Mizobe M, Noda K, Samejima M (1990) In situ perfusion system for oral mucosal absorption in dogs. J Pharm Sci 79 963-967... 

Veillard MM, Longer MA, Martens TW, and Robinson JR (1987) Preliminary studies of oral mucosal delivery of peptide drugs. J. Control. Rel. 6 123-131. 

Zhang H, Zhang J, and Streisand JB (2002) Oral mucosal drug delivery Clinical pharmacokinetics and therapeutic applications. Clin. Pharmacokinet. 41 661-680. 

An example of a simple CZE method for peptide analysis and characterization is the one developed for protegrin IB-367.37 IB-367 is a peptide containing 17 amino acid residues that possess antimicrobial properties, and it is being developed for treatment of oral mucositis associated with aggressive cancer chemotherapy as well as other topical applications. This polycationic product was chemically synthesized using solid-phase and purified by preparative reversed-phase HPLC. IB-367 is rich in cysteine and arginine residues. 

Squier, C.A., and Wertz, P.W., Structure and Function of the Oral Mucosa and Implications for Drug Delivery. In Oral Mucosal Drug Delivery (M.J. Rathbone, ed.), Marcel Dekker, Inc., New York, 1996, pp. 1-26. 

Needleman, I.G., Martin, G.P., and Smales, F.C., Characterisation of bioadhesives for periodontal and oral mucosal drug delivery, J. Clin. PeriodontoL, 25 74-82 (1998). 

Factors Affecting Systemic Oral Mucosal Delivery... 

The tolerability and safety of TCS have been evaluated in human volunteers with little indication of toxicity or sensitization. Clinical data demonstrated that TCS was not a dermal or oral mucosal irritant and was shown to have very low sensitization/allergenic potential at concentrations found in PCPs (<1%) [149]. 

Zhang Q, Nguyen AL, Shi S et al (2011) Three-dimensional spheroid culture of human gingiva-derived mesenchymal stem cells enhances mitigation of chemotherapy-induced oral mucositis. Stem Cells Dev 21(6) 937-947... 

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